Pulsatile drug delivery system for treating morning akinesia

Abstract

Provided herewith is a pharmaceutical composition comprising, separately or together, a pulsatile release component comprising levodopa and a DOPA decarboxylase inhibitor for the management of OFF-time episodes in patients with Parkinson's disease.

What is claimed is: 
     
         1 . A method of treating a motor symptom in a patient in need of treatment thereof comprising orally administering to the patient, 0 to 4 hours prior to bedtime, a pharmaceutical composition consisting of
 an amount of levodopa sufficient for treating the motor symptom;   an amount of a DOPA decarboxylase inhibitor; and   one or more excipients; wherein
 the amount of levodopa sufficient for treating the motor symptom is released from the pharmaceutical composition in one pulsatile release, after a levodopa lag time of at least 3 hours after the oral administration; 
 the amount of the DOPA decarboxylase inhibitor is released form the pharmaceutical composition in one pulsatile release after a DOPA decarboxylase inhibitor lag time of at least 3 hours after the oral administration, 
 wherein the pharmaceutical composition does not include an amount of controlled release levodopa and wherein the pharmaceutical composition does not include an amount of immediate-release levodopa. 
   
     
     
         2 . The method of  claim 1 , wherein the amount of the levodopa in the pharmaceutical composition is 1 mg to 1000 mg. 
     
     
         3 . The method of  claim 1 , wherein the amount of the levodopa in the pharmaceutical composition is 50 mg to 300 mg. 
     
     
         4 . The method of  claim 1 , wherein the amount of the DOPA decarboxylase inhibitor in the pharmaceutical composition is 1 mg to 250 mg. 
     
     
         5 . The method of  claim 1 , wherein the amount of the DOPA decarboxylase inhibitor in the pharmaceutical composition is 10 mg to 75 mg. 
     
     
         6 . The method of  claim 1 , wherein the DOPA decarboxylase inhibitor is carbidopa, benserazide, methyldopa, or α-difluoromethyl-DOPA (DFMD), or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 1 , wherein the DOPA decarboxylase inhibitor is carbidopa. 
     
     
         8 . The method of  claim 1 , wherein the pharmaceutical composition is administered to the patient 0 to 3 hours prior to bedtime. 
     
     
         9 . The method of  claim 1 , wherein the pharmaceutical composition is administered 0 to 1 hours prior to bedtime. 
     
     
         10 . The method of  claim 1 , wherein the levodopa lag time and the DOPA decarboxylase inhibitor lag time is 3 to 7 hours after the oral administration. 
     
     
         11 . The method of  claim 1 , wherein the levodopa lag time and the DOPA decarboxylase inhibitor lag time is about 4 hours after the oral administration. 
     
     
         12 . The method of  claim 1 , wherein the levodopa lag time and the DOPA decarboxylase inhibitor lag time is about 6 hours after the oral administration. 
     
     
         13 . The method of  claim 1 , wherein in said pulsatile release 70 to 100% of the amount of the levodopa is released from the pharmaceutical composition within 2 hours after the levodopa lag time, and 70 to 100% of the amount of the DOPA decarboxylase inhibitor is released from the pharmaceutical composition within 2 hours after the DOPA decarboxylase inhibitor lag time. 
     
     
         14 . The method of  claim 1 , wherein the levodopa lag time is longer than the DOPA decarboxylase inhibitor lag time. 
     
     
         15 . The method of  claim 14 , wherein the levodopa lag time is 3 to 7 hours after the oral administration and the DOPA decarboxylase inhibitor lag time is 3 to 6 hours after the oral administration. 
     
     
         16 . The method of  claim 14 , wherein the levodopa lag time is about 4 to 7 hours after the oral administration and the DOPA decarboxylase inhibitor lag time is 3 to 6 hours after the oral administration. 
     
     
         17 . The method of  claim 1 , wherein said patient in need of treatment is a patient with Parkinson's disease. 
     
     
         18 . The method of  claim 1 , wherein the motor symptom is a symptom of morning akinesia. 
     
     
         19 . The method of  claim 1 , wherein the motor symptom comprises tremor, slowness, muscle stiffness, freezing and falls, or difficulty in moving and walking in the morning.